As the administration routes of medicines, ointments or the like have been frequently used as a local administration in addition to conventional ones such as oral, injection or rectal administrations. Further in recent years, the technical development has made steady progress in transdermal application of systemically acting drugs and several kinds of drugs have come to be clinically used in practice.
Since the transdermal administration of drugs enables them to avoid the first-pass effect which they would suffer in liver, if they were orally given, drug concentration in blood is far more stable than in the case of oral or injection administration, and many advantages also can be obtained, for example, longer effective time, easier removal of the drug by detaching the preparation in case of serious side-effects, and the like.
These merits have received strong attention and changes of conventional oral route preparations to transdermal ones have been investigated on a variety of drugs.
As clinical application of the transdermal preparations has made advance, however, the difficulties and problems in the transdermal route have become clear.
Several of them are as follows:
(1) One of the most serious problems of the transdermal preparations is outbreak of local irritation and skin rash or contact dermatitis. According to a statistics, the incidence of rash is 20 to 50% by transdermal preparations of a typical occlusive type tape.
In many cases, however, the patients must use such preparations for their merits, even when the application of such preparations results in rash development.
Further, many of the drugs used clinically today are generally resistant to transdermal absorption and, even in the drugs which are transdermally absorbable, the absorption of the clinically effective amount needs enlarged application areas and combination of additives such as an absorption-promoting agent.
The enlarged application areas and the use of absorption-promoting agent and the like frequently bring about increased areas and aggravation of skin rash.
Thus, a transdermally applicable preparation which enables the absorption of a clinically effective dose of the drug with skin rash eruption inhibited is desired.
(2) In addition, while a transdermal preparation is applied for a long time, the preparation is stained or becomes peelable with time, especially bathing accelerates the removability.
It is troublesome, however, to apply a new plaster, every time the old one peels off. Moreover, the dose control becomes difficult, satisfactory efficacy cannot be attained and problems remain in appearance and hygiene.
Thus, a transdermal preparation which is resistant to staining and peeling are desired even after prolonged application.
(3) By the way, a transdermal preparation is of a sustained release type and particularly effective for chronic diseases or diseases requiring long-term treatment. And the patients with such diseases are elder people of high age in many cases. Generally, however, elder people are not good at handling which requires complicated operation.
Thus, a transdermal preparation is desired to be easy to handle for the patients, in addition to pharmaceutic satisfactions such as high absorption and the like.
Conventionally, as a plaster aiming at absorption of a clinically effective amount of a drug with skin rash inhibited, for example, the plasters according to the present inventors are known, which bear a knitted fabric of microporous hollow fibers as a constituent (WO 87/00046, WO 87/04343 and WO 90/09784).
Such plasters have been satisfactory for skin rash reduction and absorption of a clinically effective amount of a drug, but other more excellent plasters which cause no skin rash and resist peeling, even when applied for a more prolonged time, thus revealing sufficient efficacy with no problem of appearance, have been still desired.
In other words, an object of the present invention is to provide a pharmaceutical plaster which can enable the absorption of a clinically effective amount of a drug causing extremely reduced skin rash and no breakage and no peeling from the skin because of its satisfactory stretchability enough to follow skin contraction and expansion.
Another object of the present invention is to provide a pharmaceutical plaster which has excellent handleability in addition to the good absorption of a clinically effective amount of a drug, extremely reduced skin rash, no breakage and no peeling because of good stretchability to follow skin contraction and expansion.
Further, another object of the present invention is to provide a pharmaceutical plaster which can expect to develop sufficient clinical efficacy with a reduced content of a drug, when an expensive bulk such as buprenorphine or buprenorphine hydrochloride or a drug which is desired to reduce the remaining after application according to the legislation on psychopharmaceuticals handling is employed.